Fig. 6: AC484 induces potent NK and T effector cells.
From: The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity
a–e, TIL analysis from untreated, anti-PD-1-treated or AC484-treated B16 tumours. a, Representative GZMB and CD8 staining on TCRb+ cells. b, Quantifications of flow cytometry analyses showing per cent of GZMB+ CD8+ T cells (left), ratio of FOXP3− CD4+ T cells to FOXP3+ CD4+ T cells (centre) and per cent of NK1.1+ cells among CD45+ cells (right). c, Representative CD8+ T cell TOX and TIM-3 staining. d, Quantification of TIM-3 and TOX MFI and percentage of TOX+TIM-3+ CD8+ T cells as in c. e, Histograms of total STAT5 and pSTAT5 staining (left) and relative pSTAT5/STAT5 levels in B16 TILs (right). f, pSTAT5 and STAT5 expression in naive T cells treated with IL-2 (100 ng ml−1), IFNγ (1 ng ml−1), AC484 (20 μM), AC484 and IL-2, or AC484 and IFNγ in vitro with or without anti-IL-2 (2 μg ml−1) and anti-CD132 (36 μg ml−1). g, Oxygen consumption rate over time (left) and mean oxygen consumption rate (right) in naive T cells stimulated with anti-CD3/CD28. FCCP, carbonyl cyanide p-trifluoromethoxyphenylhydrazone. h, Tumour growth (left) and survival (right) of EL4-OVA tumour-bearing mice adoptively transferred with OT-I CD8+ T cells expanded in vitro in IL-2 (10 ng ml−1) with or without AC484 (100 nM). i, GZMB MFI of primary mouse NK cells co-cultured with YAC-1 tumour cells with or without AC484 in vitro (n = 8). j, NK-mediated YAC-1 tumour cell killing with or without AC484 (n = 6). k, Experimental design of in vitro chronic antigen stimulation assay on primary mouse CD8+ T cells. l, TOX and PD-1 staining on chronically stimulated CD8+ T cells. m, Per cent of chronically stimulated CD8+ T cells expressing PD-1 and TOX (left) and IFNγ and TNF (right). n, B16-OVA tumour cell viability alone (purple) or co-cultured with acutely (black) or chronically stimulated OT-I CD8+ T cells treated with AC484 (red) or DMSO (grey). Relative cytotoxicity between AC484-treated or DMSO-treated chronically stimulated CD8+ T cells, normalized to acutely (1×) stimulated T cells (right).
